Various methods have been described for the manufacture of pharmaceutical compositions which continuously release the pharmaceutical ingredients over an extended period of time. One such method is to prepare a mixture of the active ingredient and a suitable, physiologically-acceptable vehicle such as, for example, a water-insoluble colloid with which water-soluble or water-swellable colloids may be admixed, and to extrude the admixture in strands of 0.5 to 3 mm in diameter, dividing these strands into 1 to 3 mm-long cylindrical particles. A second method is to soak or coat a physiologically-suitable vehicle in the form of pellets or particles with the active ingredient.
It has however been found that, when compressing such pharmaceutical-containing particles or pellets into tablets, unexpected difficulties arise. When compressed at a relatively low pressure, the tablets, when exposed to liquid, readily disintegrate into the individual components thereof, but exhibit only low mechanical stability and abrasion resistance, which may result in damage during further preparation for market, such as during filling into blister packs or transportation in other containers. On the contrary, when higher pressures are employed during the compression process, mechanically-stable tablets are obtained which exhibit considerably-retarded disintegration characteristics, so that the pharmacokinetic properties of the tablets differ substantially from those of the individual particles.